Download Uterine Fibroids 1 Non-‐cancerous tumors called uterine

Uterine Fibroids 1 Mrs. Wilson asks, “I’ve been having heavy menstrual bleeding and severe cramping for many, many years. Should I have surgery or take medication for my fibroids?” Non-­‐cancerous tumors called uterine fibroids (leiomyomata) commonly develop in the female reproductive organ. Uterine fibroids affect as many as one in five women during their childbearing years. Risk increases with age and is higher for African American women. Often there are no symptoms associated with uterine fibroids. In some cases, women with uterine fibroids have symptoms such as pain, cramping, heavy menstrual bleeding, or negative reproductive complications such as infertility or spontaneous abortion, which may require additional treatment. These therapies can be very expensive and may result in the removal of the uterus. Treatment options of uterine fibroids include surgical, minimally invasive, and hormonal therapies or other medications. Surgical treatments such as a myomectomy or hysterectomy result in the removal of the uterine fibroid or uterus. Minimally invasive surgery can sometimes be done laparoscopically (with a camera) or by ultrasound destruction of the blood vessels that help the fibroid grow. Hormonal therapy is oftentimes combined with surgery to provide temporary or short-­‐term relief of symptoms. Due to the complexity of treatment options, further research is needed to help women target specific treatment options that effectively manage their symptom pain. Uterine Fibroids 2 Topic Brief Based on PCORI Review Criteria:
Disease Area Women’s Health •
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Suggested Research Topic What is the relative effectiveness of the available procedural or nonprocedural treatments for uterine fibroids, including: o Procedural treatments (eg, hysterectomy, myomectomy, uterine artery embolization(UAE), magnetic resonance image-­‐guided focused ultrasound, endometrial ablation) o Nonprocedural treatments (eg, hormonal therapies, oral contraceptives, and nonsteroidal anti-­‐inflammatory drugs) o Complementary and alternative medicine o Lifestyle changes o Watchful waiting (no treatment) What is the optimal sequencing of therapies, considering women's clinical characteristics and preferences? What are the most important subpopulations to predefine (eg, childbearing aim, race/ethnicity, age, and therapeutic goals)? Note: Conceptual VOI analysis(see Appendix) PCORI Criteria Brief Description RESEARCH STRATEGY: Background and Significance 1. Impact of the condition on the health of individuals and populations 1
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Uterine fibroids are the most common gynecological condition among women. •
Incidence is highest among women ages 30 to 40. •
Cumulative incidence approaches 70 percent among white women by age 50 and is even higher among African American 3
women. •
Although the tumors are benign and usually asymptomatic, they can cause pain, heavy menstrual bleeding, and anemia and are associated with a range of adverse reproductive outcomes, including infertility, spontaneous abortion, preterm birth, and 4
cesarean delivery. 2
Uterine Fibroids PCORI Criteria 3 Brief Description RESEARCH STRATEGY: Background and Significance Refers to the current impact of the condition on the health of individuals and populations. Is the condition or disease associated with a significant burden in the US population, in terms of prevalence, mortality, morbidity, individual suffering, or loss of productivity? A particular emphasis is on patients with chronic conditions, including those patients with multiple chronic conditions. Difference in Benefits •
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2. Innovation and potential for improvement •
Treatment options for symptomatic uterine fibroids include watchful waiting; nonprocedural treatments such as hormonal therapies, oral contraceptives, and nonsteroidal anti-­‐inflammatory drugs (NSAIDS); and a number of procedural treatments ranging from surgical or incisional treatments such as hysterectomy or myomectomy, to nonsurgical (also called non-­‐incisional or minimally invasive) treatments such as uterine artery embolization and 5
magnetic resonance image-­‐guided focused ultrasound. Short-­‐term medical treatment with hormonal therapy such as gonadotropin-­‐releasing hormone (GnRH) agonists is effective for reducing fibroid size prior to surgery and for reducing menstrual blood loss to provide temporary 6
symptom relief. The adverse effects of hypoestrogenism, however, limit their utility as long-­‐term treatments. Stakeholder groups have emphasized different therapeutic aims. Stakeholders also suggested that patient-­‐reported outcomes (PROs), durability of symptom relief, and reproductive outcomes were the most important outcomes to measure. For example, one therapeutic aim may be to control bleeding, while another may be to relieve pressure. An effectiveness study may use a different design, depending on the therapeutic aim of interest. Stakeholders have noted that the most important outcomes to study would vary depending on the severity of the disease in the patients under study. Conversely, the most important treatment options to study would be driven by the patient‘s treatment goals. For example, patients whose primary concerns are reproductive outcomes will not consider studies that include hysterectomy as a treatment arm. Multiple recent Cochrane reviews have reviewed the level of evidence for treatment options for uterine fibroids. In separate reviews, the evidence states: – Mifepristone reduced heavy menstrual bleeding and improved fibroid-­‐specific quality of life. However, it was not found to reduce fibroid volume. Further well-­‐designed, adequately powered randomized controlled trials (RCTs) are 7
needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. – Uterine artery embolization (UAE) appears to have an overall patient satisfaction rate similar to hysterectomy and myomectomy, while offering an advantage with regard to a shorter hospital stay and a quicker return to routine activities. However, UAE is associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. There is very low level evidence suggesting that 8
myomectomy may be associated with better fertility outcomes than UAE, but more research is needed. – There is no consistent evidence from the limited number of studies that selective estrogen receptor modulators (SERMs) reduce the size of fibroids or improve clinical outcomes. Further studies are required to establish evidence of benefit of 9
SERMs in treating women with uterine fibroids. This updated review did not find any new study for inclusion. Uterine Fibroids PCORI Criteria 4 Brief Description RESEARCH STRATEGY: Background and Significance Reduction in Uncertainty •
There are no RCTs that compare uterine fibroid embolization to vaginal hysterectomy, laparoscopic hysterectomy, or 10
laparoscopic myomectomy. •
Patient satisfaction scores after endometrial ablation are high (90 percent to 95 percent), but amenorrhea rates are much lower (15 percent to 60 percent). Data from randomized trials demonstrate that uterine fibroid embolization results in a shorter hospital stay and quicker return to work as compared with abdominal hysterectomy for leiomyomas, but after embolization, up to 20 percent of women need a second procedure. Ex-­‐ablative therapy of leiomyomas with focused ultrasound is the newest of the three methods. It has a special set of patient selection 11
criteria and is only available at fewer than 20 medical centers in the United States. Multiple literature reviews from Cochrane, Agency for Healthcare Research and Quality (AHRQ), and other researchers have concluded that there are continual gaps in information to address provider-­‐patient decision making and treatment selection. •
Probability of •
Implementation Given the limited amount of information related to treatment for uterine fibroids, probability of implementation is likely for successfully proven treatment strategies. •
However, because these procedures are performed by individuals from different subspecialties, primarily gynecologists and interventional radiologists, clinicians must consider using a multidisciplinary approach to find the best procedure for a given patient. Durability of information is likely to be very unpredictable. Technology reviews for uterine fibroids have yet to be definitive in providing options, particularly for women of childbearing age. Durability of Information •
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With such a range of symptoms and treatment options, future research may have long-­‐lasting effects on practice. Refers to the potential that the proposed research may lead to meaningful improvement in patient health, well-­‐being, or quality of care. Is the research novel or innovative in its methods or approach, in the population being studied, or in the intervention being evaluated, in ways that make it likely to change practice? Does the research question address a critical gap in current knowledge as noted in systematic reviews, guidelines development efforts, or previous research prioritizations? Has it been identified as important by patient, caregiver, or clinician groups? Do wide variations in practice patterns suggest current clinical uncertainty? Do preliminary studies indicate potential for a sizeable benefit of the intervention relative to current practice? How likely is it that positive findings could be disseminated quickly to effect changes in current practice? 3. Impact on healthcare •
Most women who have uterine fibroids will not experience symptoms severe enough to seek treatment, but for those who do, 12
uterine fibroid disease poses a significant cost and quality-­‐of-­‐life burden. Uterine Fibroids PCORI Criteria 5 Brief Description RESEARCH STRATEGY: Background and Significance performance Hysterectomy and myomectomy procedures for symptomatic uterine fibroids were estimated, using National Inpatient Sample (NIS) data, to cost upwards of $2 billion in 1997, and quality-­‐of-­‐life burden approaches that of other chronic diseases, with absenteeism 13
and disability accounting for a significant component of the cost burden. Refers to the potential that the proposed research could lead to improvements in the efficiency of care for individual patients or for a population of patients. Does the research promise potential improvements in convenience or elimination of wasted resources, while maintaining or improving patient outcomes? •
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Studies on uterine fibroids have the potential to utilize a patient-­‐centered approach. Historically, both women and physicians have been reluctant to participate in trials where hysterectomy is one of the potential treatments. Is the proposed research focused on questions and outcomes of specific interest to patients and their caregivers? Does the research address one or more of the key questions mentioned in PCORI’s definition of patient-­‐centered outcomes research? Is the absence of any particularly important outcomes discussed? •
4. Patient centeredness RESEARCH STRATEGY: Inclusiveness of Different Populations •
5. Inclusiveness of different populations Uterine fibroids span many different racial and ethnic populations, and future studies could include a range of ages, severity, racial/ethnic groups. Does the proposed study include a diverse population with respect to age, gender, race, ethnicity, geography, or clinical status? Alternatively, does it include a previously understudied population for whom effectiveness information is particularly needed? Does the study have other characteristics that will provide insight into a more personalized approach to decision making based on a patient’s unique biological, clinical, or sociodemographic characteristics? Uterine Fibroids 6 Appendix Conceptual Value of Information Analysis Information on each of the conceptual elements (eg, the expected change in uncertainty about treatment benefits from additional research and the durability of such findings) can be used to determine the population-­‐level Value of Information Analysis (VOI) from the review of evidence using existing research studies to provide informative bounds on the value of new research in individual topics without formally quantifying such VOI estimates through more complex modeling exercises. When information is available that suggests that any of these elements approximates zero, the product of these terms (and hence the VOI) will almost always be zero, unless some other element is exceptionally large (due to the multiplicative model describing VOI). For topics in which the values for the conceptual VOI are low, it is not likely that prioritizing and engaging in additional research would be an effective means of research spending14. Conceptual Element Difference in Benefits Operational Description – Potential for improvement in health outcomes, reduction of costs, and perhaps improvement in net benefits? Reduction in – Relevant studies with comparative Uncertainty information available? – Significant uncertainty in decision making? – Potential for ambiguity in evidence? Probability of – Potential for improvement in Implementation implementation by health professionals and/or patients? – Potential for overcoming financial or organizational barriers? – Potential for controversy in making decisions about best practice? – Variability in diffusion of health Assessment of Magnitude High (limited long-­‐term information comparing treatment modalities) Very High (limited assessment of effectiveness of treatment approaches) High (without strong guidance or standards for current practice, probability of implementation of successful strategies seems likely) Uterine Fibroids Durability of Information Size of Patient Population technologies and significant variation in clinical practice? – Forecasts of emergence of valuable new health technologies? – Potential for new evidence to become available? – Represents valid outcomes for clinical practice? – Significant disease burden or large proportion of patients within a specific jurisdiction? Final Assessment 7 Medium (rapidly changing field makes durability difficult to predict; information seems likely to remain relevant over time if effective) Medium (only applicable to a subset of women with symptomatic disease) Qualitative preliminary conceptual analysis suggests VOI is very likely to be greater than zero. Notes 1
Stewart EA. Uterine Fibroids. Lancet. 2001 Jan;257(9252):293–298. Baird DD, Dunson DB, Hill MC, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003 Jan;188(1):100–107. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol. 1990;94:435–438. 2
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Tristan M, Orozco LJ, Steed A, Ramírez-­‐Morera A, Stone P. Mifepristone for uterine fibroids. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD007687. DOI: 10.1002/14651858.CD007687.pub2. 8
Gupta JK, Sinha A, Lumsden M, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database of Systematic Reviews 2012, Issue 5. Art. No.: CD005073. DOI: 10.1002/14651858.CD005073.pub3. 9
Deng L, Wu T, Chen XY, Xie L, Yang J. Selective estrogen receptor modulators (SERMs) for uterine leiomyomas. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD005287. DOI: 10.1002/14651858.CD005287.pub4. 10
Stovall DW. Alternatives to hysterectomy: focus on global endometrial ablations, uterine fibroid embolization, and magnetic resonance-­‐guided focused ultrasound. Menopause. 2011; 18(4): 437–444. Uterine Fibroids 8 11
ibid Myers ER, McCrory DC, Barber MA, et al. Management of Uterine Fibroids. Evidence Report/Technology Assessment No. 34 (Prepared by Duke University under Contract No. 290-­‐97-­‐0014). Rockville, MD: Agency for Healthcare Research and Quality. July 2001. National Institute of Child Health and Human Development (NICHD), Public Information and Communications Branch. Uterine Fibroids. 2003. Viswanathan M, Hartmann K, McKoy N, et al. Management of Uterine Fibroids: An Update of the Evidence. Evidence Report/Technology Assessment No. 154 (Prepared by RTI International–University of North Carolina Evidence-­‐based Practice Center under Contract No. 290-­‐02-­‐0016.) AHRQ Publication No. 07-­‐E011. Rockville, MD: Agency for Healthcare Research and Quality. July 2007. 13
Myers ER, McCrory DC, Barber MA, et al. Management of Uterine Fibroids. Evidence Report/Technology Assessment No. 34 (Prepared by Duke University under Contract No. 290-­‐97-­‐0014). Rockville, MD: Agency for Healthcare Research and Quality. July 2001. Carls GS, Lee DW, Ozminkowski RJ, et al. What are the total costs of surgical treatment for uterine fibroids? J Womens Health. 2008;17(7):1119–1132. 14
Adapted from: Hoomans T, Seidenfeld J, Basu A, Meltzer D. Systematizing the Use of Value of Information Analysis in Prioritizing Systematic Reviews. (Prepared by the University of Chicago Medical Center through the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-­‐based Practice Center under Contract No. 290-­‐2007-­‐10058.) AHRQ Publication No. 12-­‐EHC109-­‐EF. Rockville, MD: Agency for Healthcare Research and Quality. August 2012. Available at http://www.effectivehealthcare.ahrq.gov/reports/final.cfm. 12